Efficacy of Ranolazine in Patients With Symptomatic Hypertrophic Cardiomyopathy: The RESTYLE-HCM Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: The late sodium current inhibitor ranolazine reverses the main electrophysiological and mechanical abnormalities of human hypertrophic cardiomyopathy (HCM) cardiomyocytes in vitro, suggesting potential clinical benefit. We aimed to assess the effect of ranolazine on functional capacity, symptomatic status, diastolic function, and arrhythmias in HCM. METHODS AND RESULTS: In this multicenter, double-blind, phase 2 study, 80 adult patients with nonobstructive HCM (age 53±14 years, 34 women) were randomly assigned to placebo (n=40) or ranolazine 1000 mg bid (n=40) for 5 months. The primary end point was change in peak VO2 compared with baseline using cardiopulmonary exercise test. Echocardiographic lateral and septal E/E' ratio, prohormone brain natriuretic peptide levels, 24-hour Holter arrhythmic profile, and quality of life were assessed. Ranolazine was safe and well tolerated. Overall, there was no significant difference in VO2 peak change at 5 months in the ranolazine versus placebo group (delta 0.15±3.96 versus -0.02±4.25 mL/kg per minute; P=0.832). Ranolazine treatment was associated with a reduction in 24-hour burden of premature ventricular complexes compared with placebo (>50% reduction versus baseline in 61% versus 31%, respectively; P=0.042). However, changes in prohormone brain natriuretic peptide levels did not differ in the ranolazine compared with the placebo group (geometric mean median [interquartile range], -3 pg/mL [-107, 142 pg/mL] versus 78 pg/mL [-71, 242 pg/mL]; P=0.251). Furthermore, E/E' ratio and quality of life scores showed no significant difference. CONCLUSIONS: In patients with nonobstructive HCM, ranolazine showed no overall effect on exercise performance, plasma prohormone brain natriuretic peptide levels, diastolic function, or quality of life. The drug showed an excellent safety profile and was associated with reduced premature ventricular complex burden. Late sodium current inhibition does not seem to improve functional capacity in HCM. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2011-004507-20.

Single-pixel digital holography with phase-encoded illumination.

We demonstrate imaging of complex amplitude objects through digital holography with phase-structured illumination and bucket detection. The object is sampled with a set of micro-structured phase patterns implemented onto a liquid-crystal spatial light modulator while a bucket detector sequentially records the irradiance fluctuations corresponding to the interference between object and reference beams. Our reconstruction algorithm retrieves the unknown phase information from the full set of photocurrent measurements. Interestingly, the sampling functions can be codified onto the reference beam, so they can be nonlocal with respect to the object. Finally, we show that the system is well-fitted for transmission of the object information through scattering media.

Compressive holography with a single-pixel detector.

This Letter develops a framework for digital holography at optical wavelengths by merging phase-shifting interferometry with single-pixel optical imaging based on compressive sensing. The field diffracted by an input object is sampled by Hadamard patterns with a liquid crystal spatial light modulator. The concept of a single-pixel camera is then adapted to perform interferometric imaging of the sampled diffraction pattern by using a Mach-Zehnder interferometer. Phase-shifting techniques together with the application of a backward light propagation algorithm allow the complex amplitude of the object under scrutiny to be resolved. A proof-of-concept experiment evaluating the phase distribution of an ophthalmic lens with compressive phase-shifting holography is provided.

Spatio-temporal characterization of ultrashort pulses diffracted by circularly symmetric hard-edge apertures: theory and experiment.

We carry out a complete spatio-temporal characterization of the electric field of an ultrashort laser pulse after passing through a diffractive optical element composed of several binary amplitude concentric rings. Analytical expressions for the total diffraction field in the time and spectral domain are provided, using the Rayleigh-Sommerfeld formulation of the diffraction. These expressions are experimentally validated. The spatio-temporal amplitude and phase structure of the pulse are measured at different planes beyond the diffractive optical element using spatially-resolved spectral interferometry assisted by an optical fiber coupler (STARFISH). Our results allow corroborating theoretical predictions on the presence of multiple pulses or complex spectral distributions due to the diffraction-induced effects by the hard-edge ring apertures.

Reconfigurable Shack-Hartmann sensor without moving elements.

We demonstrate wavefront sensing with variable measurement sensitivity and dynamic range by means of a programmable microlens array implemented onto an off-the-shelf twisted nematic liquid crystal display operating as a phase-only spatial light modulator. Electronic control of the optical power of a liquid lens inserted at the aperture stop of a telecentric relay system allows sensing reconfigurability without moving components. Results of laboratory experiments show the ability of the setup to detect both smooth and highly aberrated wavefronts with adequate sensitivity.

Diffractive pulse shaper for arbitrary waveform generation.

We propose an all-diffractive pulse shaper for arbitrary waveform generation in the femtosecond regime. This optical device improves in several aspects the performance of our previous quasi-direct pulse shaper reported in Mínguez-Vega et al. [Opt. Express16, 16993 (2008)]. In the present implementation, by using grayscale masks we can achieve arbitrary temporal waveforms. Additionally, the holographic reconstruction of the above masks by means of phase holograms allows for a high-efficiency shaping process. The behavior of the pulse shaper is tested by numerical simulations.

Single-shot digital holography by use of the fractional Talbot effect.

We present a method for recording in-line single-shot digital holograms based on the fractional Talbot effect. In our system, an image sensor records the interference between the light field scattered by the object and a properly codified parallel reference beam. A simple binary two-dimensional periodic grating is used to codify the reference beam generating a periodic three-step phase distribution over the sensor plane by fractional Talbot effect. This provides a method to perform single-shot phase-shifting interferometry at frame rates only limited by the sensor capabilities. Our technique is well adapted for dynamic wavefront sensing applications. Images of the object are digitally reconstructed from the digital hologram. Both computer simulations and experimental results are presented.

Fractal generalized zone plates.

The construction of fractal generalized zone plates from a set of periodic diffractive optical elements with circular symmetry is proposed. This allows us, for instance, to increase the number of foci of a conventional fractal zone plate while keeping the self-similarity property within the axial irradiance. The focusing properties of these fractal diffractive optical elements for points not only along but also in the close vicinity of the optical axis are investigated. In both cases analytical expressions for the irradiance are derived. Numerical simulations of the energetic efficiency of fractal generalized zone plates under plane wave illumination are carried out. In addition, some effects on the axial irradiance caused by variations in the area of their transparent rings are shown.

Optical filters with fractal transmission spectra based on diffractive optics.

The duality between the axial irradiance distribution originated by any circularly symmetric diffracting aperture under monochromatic illumination and its diffracted spectral intensity at a fixed on-axis point under broadband illumination is highlighted and experimentally investigated. Two applications are derived from this basic result. On the one hand, we suggest the use of a broadband source and a spectrometer for a single-shot measurement of the axial response of pupil filters. Second, we implement a spectral filter having a transmission spectrum with a fractal structure of frequencies. Experimental results and potential applications in synthetic spectra designs are provided.

Spectral analysis of femtosecond pulse diffraction through binary diffractive optical elements: theory and experiment.

We report on the changes in the spectrum of a femtosecond pulse originated by diffraction of the ultrashort waveform through a circularly symmetric binary diffractive optical element. The analysis is performed in the framework of the Rayleigh-Sommerfeld formulation of the diffraction, where an analytical expression for the monochromatic amplitude distribution close to the optical axis is obtained. To corroborate our results, we experimentally measure the variations of the pulse spectrum within the collecting area of a spectrometer located at the output plane. Multiple splitting of the pulse spectrum in the vicinity of a focal position and a phase singularity are shown.

Focusing and spectral characteristics of periodic diffractive optical elements with circular symmetry under femtosecond pulsed illumination.

The analytical solution is derived, within the Rayleigh-Sommerfeld formulation of diffraction, for the on-axis spectral irradiance of a broadband source after diffracting through a circular symmetric hard aperture. By using this solution, and within the paraxial approximation, we investigate several diffraction-induced effects originated by binary diffractive optical elements made up of a set of annular apertures with equal areas and periodic in the squared radial coordinate. In particular, the ability to focus femtosecond pulses is investigated. In addition, the analysis of the spectral modifier function associated with these elements allows us to simulate spectral shifts at focus positions. Finally, we introduce a relatively simple and low-cost technique to slice the spectrum of a broadband source in order to generate narrow bands or wavelength channels.

Efficient compensation of Zernike modes and eye aberration patterns using low-cost spatial light modulators.

Off-the-shelf spatial light modulators (SLMs) like those commonly included in video projection devices have been seldom used for the compensation of eye aberrations, mainly due to the relatively low dynamic range of the phase retardation that can be introduced at each pixel. They present, however, some interesting features, such as high spatial resolution, easy handling, wide availability, and low cost. We describe an efficient four-level phase encoding scheme that allows us to use conventional SLMs for compensating optical aberrations as those typically found in human eyes. Experimental results are obtained with artificial eyes aberrated by refractive phase plates introducing either single Zernike terms or complex eye aberration patterns. This proof-of-concept is a step toward the use of low-cost, general purpose SLMs for the compensation of eye aberrations.

Dispersion-compensated beam-splitting of femtosecond light pulses: Wave optics analysis.

Recently, using parageometrical optics concepts, a hybrid, diffractive-refractive, lens triplet has been suggested to significantly improve the spatiotemporal resolution of light spots in multifocal processing with femtosecond laser pulses. Here, we carry out a rigorous wave-optics analysis, including the spatiotemporal nature of the wave equation, to elucidate both the spatial extent of the diffractive spots and the temporal duration of the pulse at the output plane. Specifically, we show nearly transform-limited behavior of diffraction maxima. Moreover, the temporal broadening of the pulse is related to the group velocity dispersion, which can be pre-compensated for in practical applications. Finally, some numerical simulations of the spatiotemporal wave field at the output plane in a realistic case are provided.

On-axis diffraction of an ultrashort light pulse by circularly symmetric hard apertures.

The analytical solution of the Rayleigh-Sommerfeld on-axis diffraction integral for an ultrashort light pulse diffracted by circularly symmetric hard apertures is derived. The particular case of a circular aperture is treated in detail. The time changes of the instantaneous intensity along the axial direction are predicted. An analysis of the standard deviation width shows a pulse broadening about the axial positions where the instantaneous intensity reaches a zero value. We show that the temporal shape of the instantaneous intensity depends on the number of oscillation cycles at the central frequency of the real electric field.

Measurement and compensation of optical aberrations using a single spatial light modulator.

We describe a compact adaptive optical system using a spatial light modulator (SLM) as a single element to both measure and compensate optical aberrations. We used a low-cost, off-the-shelf twisted nematic liquid-crystal display (TNLCD) optimally configured to achieve maximum phase modulation with near constant transmittance. The TNLCD acts both as the microlens array of a Hartmann-Shack wavefront sensor and as the aberration compensation element. This adaptive setup is easy to implement and offers great versatility.

Chromatic compensation of broadband light diffraction: ABCD-matrix approach.

Compensation of chromatic dispersion for the optical implementation of mathematical transformations has proved to be an important tool in the design of new optical methods for full-color signal processing. A novel approach for designing dispersion-compensated, broadband optical transformers, both Fourier and Fresnel, based on the collimated Fresnel number is introduced. In a second stage, the above framework is fully exploited to achieve the optical implementation of the fractional Fourier transform (FRT) of any diffracting screen with broadband illumination. Moreover, we demonstrate that the amount of shift variance of the dispersion-compensated FRT can be tuned continuously from the spatial domain, which is totally space variant, to the spectral domain, which is totally space invariant, with the chromatic correction remaining unaltered.